Generation and characterization of a novel shoulder contracture mouse model

Abstract

Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self-limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes.

Characterization of a frozen shoulder model using immobilization in rats

“…The current state of knowledge reflects a poor understanding of the etiology and pathologic mechanism for frozen shoulder [7, 8, 14]. Histologically, Ozaki et al [6] and Bunker et al [13] reported that fibrosis of the capsule was the main lesion, but neither inflammation nor synovitis was observed [15].…”

“…To date, seven studies describing the development of animal frozen shoulder models using canine, rat, or mouse have been reported [14–20]. The optimal choice of animal and methodology that would be most useful in creating a model for frozen shoulder remains unclear.…”

“…Despite intensive efforts, however, the underlying pathophysiologic process of frozen shoulder is not yet fully elucidated. Therefore, the development of animal models of frozen shoulder would seem to be essential in order to further characterize the underlying pathophysiology of frozen shoulder and the subsequent development of relevant therapeutic targets [14]. …”

“…Although animal frozen shoulder models using mouse, rat, or canine have been developed [14–20], a rat shoulder contracture model using immobilization has been among the most frequently established due to similarities with human anatomy and a high levels of reproducibility [15–17, 20]. However, few studies have been conducted to investigate the serial pathophysiologic changes to the glenohumeral joint following immobilization while developing such animal frozen shoulder models.…”

The Serum from Patients with Secondary Frozen Shoulder Following Rotator Cuff Repair Induces Shoulder Capsule Fibrosis and Promotes Macrophage Polarization and Fibroblast Activation

“…Ten days after the procedure, mice were euthanized by CO 2 overdose to harvest their left shoulders. Immediately following sample collection, passive ROM was measured using the manner reported by Oki et al 33 Then, the samples were fixed in 10% neutral buffered formalin for one day, and were decalcified, dehydrated, and embedded in paraffin wax for histological examination. HE and Masson staining were conducted based on the established method.…”